Staphylococcus epidermidis is a major component of the normal human microbial flora on the skin and mucous membranes and was once considered only a contaminant when cultured from an infected patient. See Heilmann, C. and G. Peters, Biology and pathogenicity of Staphylococcus epidermidis, in Gram-positive pathogens, V. A. Fischetti, Editor. 2000, American Society for Microbiology: Washington, D.C. p. 442-449; von Eiff, C., et al., Lancet Infect Dis, 2(11): p. 677-85 (2002). It is now widely accepted to be an opportunistic pathogen of great importance and a leading cause of nosocomial bloodstream infections. See Am J Infect Control, 27: p. 520-32 (1999); Diekema, D. J., et al., Int J Antimicrob Agents, 20(6): p. 412-8 (2002); Edmond, M. B., et al., Clin Infect Dis, 29(2): p. 239-44 (1999). These infections are primarily associated with the presence of an indwelling foreign polymer body such as a venous catheter, prosthetic joint or prosthetic heart valve. See Heilmann, C. and G. Peters, Biology and pathogenicity of Staphylococcus epidermidis, in Gram-positive pathogens, V. A. Fischetti, Editor. 2000, American Society for Microbiology: Washington, D.C. p. 442-449; von Eiff, C., et al., Lancet Infect Dis, 2(11): p. 677-85 (2002). Infection is thought to result from introduction of Staphylcoccus epidermidis from the patient's skin upon insertion of the prosthetic device. Colonization and subsequent biofilm formation can lead to bacteremia with the potential for hematogenous spread to other sites in the body. These infections are often difficult to treat, arising from the reduced killing of bacteria within a biofilm by antibiotics and also an increase in antibiotic resistance among clinical isolates. See Diekema, D. J., et al., Int J Antimicrob Agents, 20(6): p. 412-8 (2002); Edmond, M. B., et al., Clin Infect Dis, 29(2): p. 239-44 (1999); Lewis, K., Antimicrob Agents Chemother, 45(4): p. 999-1007 (2001); Raad, I. et al., Clin Infect Dis, 26(5): p.1182-7 (1998). Staphylcoccus epidermidis with reduced susceptibility to vancomycin have been reported. See Sanyal, D. and D. Greenwood, J Med Microbiol, 39(3): p. 204-10(1993); Sanyal, D., et al., Lancet, 337(8732): p. 54(1991). Difficulty treating these infections necessitates the use of immunization as a means to prevent infection.
Biofilm formation is a major virulence determinant for Staphylcoccus epidermidis infections. Consequently, research on Staphylcoccus epidermidis surface proteins has focused on those proteins involved in biofilm formation. These proteins have been subdivided into groups based on their involvement in the two major steps of biofilm formation: 1) primary attachment, staphylococca; surface protein-1 (SSP-1), autolysin (AtIE), Fbe (SdrG) and GehD and 2) bacterial cell accumulation, Bap homologous protein (Bhp), accumulation associated protein (AAP) and autolysin (AtIE). See von Eiff, C., et a., Lancet Infect Dis, 2002. 2(11): p. 677-85; Vuong, C., et al., J Infect Dis, 188(5): p. 706-18 (2003); Veenstra, G. J., et al., J Bacteriol., 178(2): p. 537-41 (1996); Rupp, M. E., et al., J Infect Dis, 183(7): p. 1038-42 (2001); Hussain, M., et al., Infect Immun, 65(2): p. 519-24 (1997); Nilsson, M., et al., Infect Immun, 66(6): p. 2666-73 (1998); Davis, S. L., et al., J Biol Chem, 276(30): p. 27799-805 (2001); and Bowden, M. G., et al., J Biol Chem, 277(45): p. 43017-43023 (2002). Comparatively less effort has been exerted towards the identification of surface proteins expressed upon exposure to the environmental cues within the host or those involved in host-parasite interactions.
Staphylcoccus epidermidis must undergo a transition from commensal to pathogen and adapt to its microenvironment within the host. For a commensal to transition to a pathogen it must gain access to host tissue, sense changes in its environment, alter gene expression so that it is able to evade host defenses, attach and adhere to host factors, grow and divide in the presence of different nutrients and host defenses. Proteins on the bacterial surface make initial contact with the new environment within the host. The many functions of these proteins include sensing the environment, scavenging and transporting nutrients, defending against the host immune system and binding host proteins. Surface exposed proteins can also serve as points of contact or recognition by the host immune system and can be targets for a humoral immune response against the bacterium. Josefsson, E., et al., J Infect Dis, 184(12): p. 1572-80 (2001); Swiatlo, E., et al., Infect Immun, 71(12): p. 7149-53 (2003); Grifantini, R., et al., Nat Biotechnol, 20(9): p. 914-21 (2002). Thus, there is an immediate need for identifying promising candidates among Staphylococcus epidermidis proteins for use in immunogenic compositions that induce immune responses to disease causing serotypes of Staphylococcus epidermidis. 